P-116: The impact of SLiM criteria in myeloma in a real-life population: clinical characteristics, treatment and outcome from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR)

Background

In addition to 4 CRAB criteria, 3 biomarkers were adopted as myeloma-defining events: clonal marrow plasma cell (PC) percentage ≥60%, serum free light chain ratio (SFLCR) ≥100 and >1 MRI focal lesion, known as SLiM (SixtyLightchainMRI), but there has been no analysis of their clinical impact.

Methods

We compared the characteristics, treatment & outcomes of 1686 pts diagnosed by CRAB and 132 pts by SLiM enrolled in the MRDR from 2013 - 2018, to assess the impact of these criteria on clinical practice and treatment outcomes.

Results

Patient & Disease characteristics. In 132 SLiM pts, 48 had SFLCR≥100, 58 BMPC>60% and 26 were known to have both, nil had MRI lesions (limited by MRI availability). CRAB pts included a higher proportion with advanced stage ISS-3 (35.6% v 10.7%, p <0.001), R-ISS-3 (16.0% v 2.5%, p=0.001) and poor performance status (ECOG 2 to 4: 24.7% v 8.3%, p<0.001). Renal impairment was more prevalent in CRAB vs SLiM (eGFR 67 v 79 ml/min, p<0.001) and median Hb was lower (108 v 117 g/L, p<0.001). Median BM PC (60% v 50%, p = 0.004) and SFLCR (100 v 39; p<0.001) were higher in SLiM than CRAB. There was also a trend for a higher incidence of FISH anomalies in CRAB v SLiM - 65.8% v 55.3% (p=0.07).

Outcomes

OS was longer in SLiM than CRAB (median 76.3 v 65.2 m, p=0.02, HR 1.75), with no difference in PFS (30.8 v 30.2 m, p=0.30, HR 1.17). However PFS2 was superior for SLiM of 48.7 m v 38.2 m for CRAB (HR 1.38, p=0.06). No difference in best response rates (≥PR & ≥VGPR) was seen in SLiM v CRAB. Within SLiM, comparing 3 groups: those who satisfied the criteria of SFLCR>100 only (SFLC group, n=28), PC≥60% only (PC group, n=34) or both (n=20), pts with <PR was 3.6% in SFLC group, 17.6% in PC group, and 20% for pts with both (p=0.04), indicating that pts who satisfy PC criteria (alone or together with SFLCR) have a higher risk for suboptimal response.

Discussion

We found differences in characteristics between SLiM and CRAB pts – higher BM PC infiltration and SFLCR in SLiM, and a trend for higher incidence of FISH anomalies in CRAB. SLiM pts had a median OS 11.1 m longer than CRAB, but no difference in PFS1 or response rates. The OS difference of -1 yr could reflect the earlier initiation of therapy in SLiM. However the trend for a longer PFS2 for SLiM indicates improved treatment outcome to therapy at first relapse, suggesting the shorter PFS2 of CRAB pts may result from residual or re-emerging drug-resistant clones.

Conclusions

In a real-life population our findings support the benefit of earlier initiation of therapy by SLiM criteria, with an improved OS and a trend towards improved outcome at first relapse (PFS2). Patients with PC criteria in the SLiM cohort have an increased risk for suboptimal response compared to those who satisfy SFLC criteria alone.